Principal Investigator
Jane C.
Figueiredo
Awardee Organization
Cedars-Sinai Medical Center
United States
Fiscal Year
2023
Activity Code
U54
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date
NIH RePORTER
For more information, see NIH RePORTER Project 3U54CA260591-02S3
Diversity and Determinants of the Immune-Inflammatory Response to SARS-CoV-2
ASBTRACT Overview Every day, Californians continue to experience high levels of exposure to the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) virus. There is an ever-growing urgent need to better understand the nature of exposures, course of illness and recovery, and potential for immunity among persons at particularly heightened risk for the worst COVID-19 outcomes. As part of a rapid scientific response to the present public health crisis, we convened on March 18, 2020 a collaborative of frontline clinicians and scientists to form the Coronavirus Risk Associations and Longitudinal Evaluation (CORALE) studies (corale-study.org). We established two base study cohorts with enrollment centered on (i) patients with suspected or confirmed COVID-19 treated in our health system (currently N>8,300) and on (ii) healthcare workers directly or indirectly involved in delivering their care (currently N=6,679). In response to NIH RFA-CA-20-038, we are now highly motivated and prepared to leverage our existing infrastructure to directly address the critical need for comprehensive longitudinal data collection and analyses to advanced our understanding of SARS-CoV-2 risks, the course of disease, the nature of recovery, and the potential for immunity across populations at risk. By establishing the CORALE-SeroNet U54 program, our goal will be to form a robust and sustainable structure of academic activities centered on investigating the responses elicited by SARS-CoV-2 exposure and the extent to which carefully phenotyped clinical and molecular profiles can signal robust immune reconstitution and complete functional recovery. Our study will be centered on the ethnically/racially diverse population served by our health system in Los Angeles, given then critical need for more knowledge regarding the determinants of COVID-19 related risks in these minority subgroups. Our scientific objectives will be achieved by an outstanding collaborative team of clinician-scientists, epidemiologists, immunologists, basic and translational scientists, analytical chemists, and biostatisticians. Leveraging our collective experience, resources, and infrastructure at major academic institutions from across Southern California (Cedars Sinai, UCSD, UCLA, and USC), we will advance the scientific enterprise through the three distinct yet closely integrated research Projects: Project 1 will elucidate the natural history and longitudinal trajectories that represent the diversity of SARS-CoV-2 exposure, infection, recovery, and clinical immunity patterns across the spectrum of persons at risk. Project 2 will investigate the determinants of SARS-CoV-2 response in persons with altered innate immune function, with a focus on individuals with pre-infection susceptibility traits (e.g. metabolic disease states); and, Project 3 will investigate the determinants of SARSCoV-2 response in persons with altered adaptive immune function, with a focus on individuals with immunealtered status arising from select malignancies, autoimmune disease, and/or their directed therapies. As a whole this research program will integrate population, clinical, translational, and basic science resources with a worldclass investigator team to meet the urgent need for new mechanistic insights and therapeutic approaches to address key knowledge gaps regarding SARS-CoV-2 susceptibility and potential for immunity.
Publications
- Xian H, Liu Y, Rundberg Nilsson A, Gatchalian R, Crother TR, Tourtellotte WG, Zhang Y, Aleman-Muench GR, Lewis G, Chen W, Kang S, Luevanos M, Trudler D, Lipton SA, Soroosh P, Teijaro J, de la Torre JC, Arditi M, Karin M, Sanchez-Lopez E. Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation. Immunity. 2021 Jul 13;54(7):1463-1477.e11. Epub 2021 Jun 10. PMID: 34115964
- Xu AM, Li D, Ebinger JE, Mengesha E, Elyanow R, Gittelman RM, Chapman H, Joung S, Botwin GJ, Pozdnyakova V, Debbas P, Mujukian A, Prostko JC, Frias EC, Stewart JL, Horizon AA, Merin N, Sobhani K, Figueiredo JC, Cheng S, Kaplan IM, McGovern DPB, Merchant A, Melmed GY, Braun J. Differences in SARS-CoV-2 Vaccine Response Dynamics Between Class-I- and Class-II-Specific T-Cell Receptors in Inflammatory Bowel Disease. Frontiers in immunology. 2022 Apr 8;13:880190. doi: 10.3389/fimmu.2022.880190. eCollection 2022. PMID: 35464463
- Sobhani K, Cheng S, Binder RA, Mantis NJ, Crawford JM, Okoye N, Braun JG, Joung S, Wang M, Lozanski G, King CL, Roback JD, Granger DA, Boppana SB, Karger AB. Clinical Utility of SARS-CoV-2 Serological Testing and Defining a Correlate of Protection. Vaccines. 2023 Oct 26;11. (11). PMID: 38005976